Journal article

The evolutionary landscape of colorectal tumorigenesis.

  • Cross W Evolution and Cancer Laboratory, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Kovac M Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Mustonen V Organismal and Evolutionary Biology Research Programme, Department of Computer Science, Institute of Biotechnology, Helsinki Institute for Information Technology HIIT, University of Helsinki, Helsinki, Finland.
  • Temko D Evolution and Cancer Laboratory, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Davis H Gastrointestinal Stem Cell Biology Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Baker AM Evolution and Cancer Laboratory, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Biswas S Gastrointestinal Stem Cell Biology Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Arnold R Cancer Bioinfomatics Group, Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
  • Chegwidden L Gastrointestinal Cancer Genetics Laboratory, Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
  • Gatenbee C Integrated Mathematical Oncology Department, Moffitt Comprehensive Cancer Centre, Tampa, FL, USA.
  • Anderson AR Integrated Mathematical Oncology Department, Moffitt Comprehensive Cancer Centre, Tampa, FL, USA.
  • Koelzer VH Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Martinez P Evolution and Cancer Laboratory, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Jiang X Cancer Genetics and Evolution Laboratory, Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
  • Domingo E Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Woodcock DJ Big Data Institute, University of Oxford, Oxford, UK.
  • Feng Y Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Kovacova M Institute of Mathematics and Physics, Faculty of Mechanical Engineering, Slovak University of Technology in Bratislava, Bratislava, Slovakia.
  • Maughan T Department of Oncology, University of Oxford, Oxford, UK.
  • Jansen M Department of Research Pathology, Cancer Institute, University College London, London, UK.
  • Rodriguez-Justo M Department of Surgery, University Hospitals Birmingham, Birmingham, UK.
  • Ashraf S Department of Colorectal Surgery, Cancer Centre, Churchill Hospital, Oxford University Hospital NHS Foundation Trust, Oxford, UK.
  • Guy R Department of Colorectal Surgery, Cancer Centre, Churchill Hospital, Oxford University Hospital NHS Foundation Trust, Oxford, UK.
  • Cunningham C Translational Gastroenterology Unit, University of Oxford, John Radcliffe Hospital, Oxford, UK.
  • East JE Big Data Institute, University of Oxford, Oxford, UK.
  • Wedge DC Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Wang LM Gastrointestinal Cancer Genetics Laboratory, Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
  • Palles C Institute for Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
  • Heinimann K Evolutionary Genomics and Modelling Lab, Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK.
  • Sottoriva A Gastrointestinal Stem Cell Biology Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Leedham SJ Evolution and Cancer Laboratory, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK. t.graham@qmul.ac.uk.
  • Graham TA Cancer Genetics and Evolution Laboratory, Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. i.tomlinson@bham.ac.uk.
  • Tomlinson IPM
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  • 2018-09-05
Published in:
  • Nature ecology & evolution. - 2018
English The evolutionary events that cause colorectal adenomas (benign) to progress to carcinomas (malignant) remain largely undetermined. Using multi-region genome and exome sequencing of 24 benign and malignant colorectal tumours, we investigate the evolutionary fitness landscape occupied by these neoplasms. Unlike carcinomas, advanced adenomas frequently harbour sub-clonal driver mutations-considered to be functionally important in the carcinogenic process-that have not swept to fixation, and have relatively high genetic heterogeneity. Carcinomas are distinguished from adenomas by widespread aneusomies that are usually clonal and often accrue in a 'punctuated' fashion. We conclude that adenomas evolve across an undulating fitness landscape, whereas carcinomas occupy a sharper fitness peak, probably owing to stabilizing selection.
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